Effects Of RhTNF-α And Bcl-2 Atisense Oligodeixynucleotides On Proliferation And Apoposis Of HL60 And Ca46

OBJECTS Apoptosis of malignant cell is under regulation of many genes and their expressions. These genes and expressions consist of a complicated network in which they can make some effects on each other. Through using some cytokines and gene theraputic drugs interfering with this network, development of malignances may be depressed. In order to learn more about the relationship between TNF- a and bcl-2 on the hemotological malignances apoptosis regulation , proliferation and apoptosis of acute myeloid leukemic cell line HL60 and lymphomatous cell line Ca46 which were treated with rhTNF- a and bcl-2 antisense oligodeoxynucleotides(ASO) were investigated. The paper was divided into two pieces in order to explain the outcomes on HL60 and Ca46 separately. METHODS The synergistic effects of rhTNF-a and bcl-2 antisense oligodeosynucleotides on the proliferation and apoptosis of leukemic cellline HL60 and lymphomatous cell line Ca46 were studied by using trypan blue exclusive cell counting, MTT assays, colony formation, flow cytometer(FCM) technique and in situ cell apoptosis detection. We also detect the variation of bcl-2 oncogene expression through verse transcription-polymerase chain reaction(RT-PCR) and immunohistochemical staining.RESULTS Both rhTNF-a and bcl-2 ASO can inhibit the proliferation and induce the apoptosis of HL60 and Ca46. These effects can be significantly augumented by the combinative therapy. A sharply down-regulation of bcl-2 oncogene expression can also be observed.CONCLUSIONS 1. Cytokine TNF-a in combination with bcl-2 ASO probably has synergistic effects on hematological malignances apoptosis; 2. Down-regulation of bcl-2 oncogene expression may be an important factor on the apoptosis of malignances by this combinative therapy; 3. Significant effects can be seen in both H1L60 and Ca46, so the regimen combined with rhTNF-a and bcl-2 ASO may be useful in various hematological malignances. In a word, regimens including cytokine and antisense oligodeoxynucleotides may provide a new theraputic approach for hematological malignancies.